Telomere and telomerase are key factors that regulate cell replicative lifespan. Telomere shortening has been observed in many types of cells in vitro and in cross-sectional analyses, and significantly shortened telomeres induce cell senescence and apoptosis. However, it remains to be determined how telomere length change in vivo and whether dysfunctional shortened telomeres contribute to age-associated decline of function. To address these questions, we conducted a longitudinal analysis of 1) lymphocyte subset composition, 2) telomere length of peripheral blood lymphocytes (T and B cells) and monocytes and 3) telomerase expression in peripheral blood T cells (at rest and after activation) of approximately 200 individuals (starting age from 30s to late 80s). Age-associated changes were observed in lymphocyte subsets and telomere length but not in telomerase activity. Longitudinally, no obvious changes in young group (starting age under 45 year old), and several changes including telomere shortening in the old group (starting age over 70 year old) in 5 year life span. Together, these findings demonstrated that the rates of telomere attrition in blood lymphocytes and monocytes in vivo differ significantly in young and old individuals. Currently, we initiated a clinical study to test the hypothesis that individuals who have shortened telomeres are impaired in mounting an effective immune response. The physiological significance of the length of telomeres in the overall immune function is under current investigation.